Safety and Effectiveness of a Three-Drug Combination Treatment for Recently Infected or Converted HIV Patients

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00007202
First received: December 15, 2000
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to determine the safety and effectiveness of stavudine (d4T), didanosine (ddI), and BMS-232632 when given early in the course of HIV infection.

Acute HIV infection may develop in patients that are exposed to the HIV virus. Following infection, the viral load (level of HIV in the blood) rises rapidly over the next few days to weeks. It is not known which is the best treatment in patients with very early HIV infection. Researchers believe these patients may respond well to strong early treatment. A combination consisting of enteric-coated didanosine (ddI-EC), stavudine (d4T), and the HIV-1 protease inhibitor, BMS-232632, will be tested.


Condition Intervention Phase
HIV Infections
Drug: Atazanavir
Drug: Stavudine
Drug: Didanosine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Pilot Open-Label Phase II Clinical Trial to Evaluate the Safety and Efficacy of a Compact Three Drug Antiretroviral Treatment Regimen for Subjects With Acute HIV-1 Infection or Recent HIV-1 Seroconversion

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Enrollment: 55
Study Completion Date: October 2006
Detailed Description:

Acute primary HIV-1 infection (PHI) follows exposure to the HIV-1 virus and results in a rapid rise in plasma viremia within days to 1 to 3 weeks. Individuals with acute PHI or early HIV-1 infection represent a potentially unique patient population in which to evaluate potent antiretroviral therapies because of the degree of viral heterogeneity and the fact that immunologic disruption is likely to be lower than in later stages of HIV-1 disease. The optimal treatment for acute PHI is unknown. This study evaluates a regimen consisting of enteric-coated didanosine (ddI-EC), stavudine (d4T), and the HIV-1 protease inhibitor, BMS-232632.

Patients are enrolled into Group I or Group II and may participate in substudies. Patients in Group I receive ddI-EC, d4T, and BMS-232632 daily for 52 weeks. Clinical, virologic, and immunologic evaluations are performed on Days 2, 7, 14, 21, and 28, then every 4 weeks through Week 24, and then every 8 weeks thereafter through Week 48. Based on laboratory results from the Week 48 visit, a decision is made by Week 52 whether or not to continue study medications for an additional 52 weeks. Evaluation schedules for those patients enrolled in substudies may be different. Group II patients elect not to receive antiretroviral treatment and are followed as a natural history disease group to be compared with patients in Group I. They are followed according to the same schedule of evaluations as those enrolled in Group I, unless otherwise specified as part of their participation in substudies. All patients are followed in this study at 8-week intervals for a total duration of 104 weeks (2 years). HIV will be measured in plasma and tissues to determine reduction in replication for a duration of at least 48 weeks.

The 3 substudies in which patients may participate are AI-03-006, Lymphoid Tissue Substudy; AI-03-007, Immunology Substudy of cytolytic and co-stimulatory markers, T-cell repertoire, and cytokine and chemokine elaboration; and AI-03-008, Viral Dynamics and Diversity Substudy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Have early HIV infection or show recent seroconversion (going from HIV-negative to HIV-positive).
  • Are at least 18 years old.
  • Agree to 2 barrier methods of birth control, if heterosexually active men or women, during the study and for 3 months after.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have received prior antiretroviral therapy.
  • Have received interferons, interleukins, colony-stimulating factors, radiation, cytotoxic chemotherapy, or HIV vaccines within 30 days prior to study entry.
  • Have had any experimental therapy within 30 days prior to study entry.
  • Are pregnant or breast-feeding.
  • Patients will not be eligible for Group I if they:
  • Have had pancreatitis (inflammation of the pancreas).
  • Have received alpha tocopherol (vitamin E), amiodarone, astemizole, carbamazepine, cisapride, ergotamine/diergotamine, estrogens, fluvastatin, glucocorticoids, itraconazole, ketoconazole, midazolam, phenobarbital, phenytoin, quinidine, rifampin, rifabutin, sildenafil, statin drugs (simvastatin, pravastatin, atorvastatin) used for reduction of triglyceride or cholesterol levels, terfenadine, triazolam, or warfarin within 14 days of study entry.
  • Have received chloramphenicol, cisplatin, clioquinol, dapsone, diphenylhydantoin, disulfiram, ethionamide, glutethimide, gold, hydralazine, isoniazid, metronidazole, pyridoxine, sodium cyanate, thalidomide, vincristine, or zalcitabine within 30 days of study entry. In certain cases, patients taking these drugs may still be eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00007202

Locations
United States, Colorado
Univ. of Colorado Health Sciences Ctr. AIEDRP
Denver, Colorado, United States, 80262
United States, Georgia
AIDS Research Consortium of Atlanta, Inc. (ARCA) AIEDRP CRS
Atlanta, Georgia, United States, 30308
United States, Illinois
Rush Univ. Med. Ctr., Dept. of Infectious Disease AIEDRP CRS
Chicago, Illinois, United States, 60612
Feinberg School of Medicine, HIV/ACTU AIEDRP CRS
Chicago, Illinois, United States, 60611-3015
Brazil
Centro de Referencia Estadual de AIDS AIEDRP
Salvador, Bahia, Brazil
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: Constance Benson
Study Chair: Robert Schooley
Study Chair: Wheaton Williams
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00007202     History of Changes
Other Study ID Numbers: AI-03-005, 10431, AIEDRP AI-03-005, Substudy AI-03-006, Substudy AI-03-007, Substudy AI-03-008
Study First Received: December 15, 2000
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Virus Replication
HIV-1
Didanosine
Drug Therapy, Combination
Stavudine
HIV Protease Inhibitors
Sensitivity and Specificity
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Reverse Transcriptase Polymerase Chain Reaction
Acute Infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Stavudine
Reverse Transcriptase Inhibitors
Atazanavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014